Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Studies toward the synthesis of the shark repellent pavoninin-5

Sharks are the most dangerous predators of people in the sea, resulting in people being mauled and killed each year. A shark repellent could help to diminish this danger. The aglycone of the shark repellent pavoninin-5, (25R)-cholest-5-en-3β,15α,26-triol (5a), was synthesized from diosgenin (9). Removing mercury from the Clemmensen reduction of 9 gave a higher yield of (25R)-cholest-5-en-3β,16β,26-triol, 10a, and was also more environmentally friendly. Attempted methods for the transposition of the C-16β hydroxyl to the 15α position are described. A successful method for this transposition via the 15α-hydroxy-16-ketone, 8a, using the Barton deoxygenation reaction on the 16-alcohol 14b, is reported.     

In-situ observations of phase transformations in titanium

An in-situ laser-scanning confocal microscopy study has been undertaken on the phase transformations in highpurity titanium. Observations of the β-Ti to α-Ti were observed to proceed with a pronounced Widmanstätten plate morphology due to the large β-Ti grain size. An anomalous transformation was also observed, with the α-Ti growing with a defined ledge-like surface relief. The observed transformation morphologies are discussed with reference to the crystallography of the regions, analyzed using electron-backscatter diffraction.     

The mental health arena.

If C. A. Kiesler's (1977) comparative analysis of the training of psychologists vs psychiatrists proves to be true after closer inspection, this analysis can document that doctoral-level psychologists have as much (or more) training as psychiatrists yet receive considerably less income. The reasons that psychiatrists dominate mental health settings are reviewed, and it is argued that the mythical nature of the public's collective approaches to physicians should be exposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Properties of an elementary class of fluids with nondissipative viscous stresses

A class of fluids with both dissipative and nondissipative viscous stresses is analyzed. The class is delineated by the three assumptions, (1) the stress is isotropic, (2) the fluid admits no natural time scale, (3) the Stoke's assumption, tr(t) = − 3p, is satisfied. The constitutive relations are shown to be uniquely determined in terms of the linear bulk viscosity and the linear shear viscosity. The characteristic features of such fluids are obtained and experimental distinguishability between these fluids and the classic Navier-Stokes fluid is examined in detail. In general, it is surprisingly difficult to distinguish between the fluids considered here and the classic Navier-Stokes fluids, even though there are characteristic anomalies associated with the nondissipative stresses.     

On the functional forms of activity coefficients and their properties

A complete system of partial differential equations is obtained for the logarithms of activity coefficients of real chemical mixtures. All solutions of these equations are obtained under mild regularity conditions and the conditions that the limit of ln (f_α), as n_α/n tends to unity, is equal to zero. It is shown that all of the functions ln (f_α) can be determined if any one of them is a known function of temperature, pressure and the independent mole fractions. These results are used to compute the deviations of partial and total volume, entropy and specific heats at constant pressure, and the laws of mass action from what would be given for ideal mixtures. Conditions for static and dynamic stability of equilibrium are obtained, and a forward time integration procedure is given for satisfaction of the laws of mass balance and the full form of the laws of mass action.     

On a closure of the governing equations of defect dynamics and the resulting theory of the plastic state

The equations of defect dynamics are derived from the single system of relations that specifies the time rate of change of the dislocation densities. The resulting source equations are shown to admit a 12-fold gauge group and the resulting kinematic equations are shown to admit a 15-fold gauge group. The generators of the two gauge groups are determined by the requirements that the Burgers and Frank vectors have their classical representations. This determination results in a unique decomposition of all quantities in terms of sums of internal variables and external geometric variables, and represents the first and second closures of the field equations. The presence of a unique external system of geometric variables permits derivation of the forms of the equations of balance of mass, momentum, moment of momentum and energy. The third closure is obtained through use of the practices of nonequilibrium thermodynamics. This results in a system of equations that determines the dislocation currents in terms of the distortion, the dislocation density and the geometric strain measures. A class of models is exhibited wherein most of the properties of plasticity theories are obtained.     

Programs for computer implementation of the exterior calculus with applications to isovector calculations

Program listings are given in the REDUCE 2 Algebraic Programming system that implement the following operations of the exterior calculus: exterior multiplication, exterior differentiation, inner multiplication, Lie differentiation, and Lie multiplication. These programs realize exterior forms and vector fields by resolving them on unevaluated systems of operators with the necessary algebraic properties. Use of these programs in the computation of isovectors of ideals of exterior forms is illustrated for the case where the ideal is generated by the system of exterior forms of degree two that characterize the equations for shallow water waves.     

The net effect of ultraviolet radiation on atmospheric dimethylsulphide over the Southern Indian Ocean

Dimethylsulphide (DMS) in the atmosphere may play an important role in the climate system. This study shows an inverse relationship between ultraviolet extremes and atmospheric DMS, independent of changes in wind speed, sea-surface temperature and photosynthetically active radiation, as measured at Amsterdam Island in the Southern Indian Ocean.     

Thermodynamic analysis of arsenic methylation

The Challenger mechanism for the methylation of arsenic is a repeating sequence of a two-electron reduction of pentavalent arsenic As(V) species to trivalent arsenic As(III) species followed by a methylation-oxidation reaction forming the successive methyl As(V) species. This unusual oxidation-reduction sequence prompted an examination of the thermodynamics of these reactions. Quantum chemical methods are employed to estimate the thermodynamic parameters for the methyl arsenic species. The sequence is thermodynamically favored at neutral pH for redox potentials with pe < 0 and methyl cation activities pCH3+ < -3 to -7 depending on the precise situation analyzed. The observed distribution of methyl arsenic species in human urine, which is remarkably constant across many studied populations, can be reproduced using an equilibrium model if the formation of TMA species is prevented. The estimated thermodynamic parameters are sufficiently accurate to evaluate questions of thermodynamic plausibility but not the precise details of speciation.